The Effective medical treatment of inner ear disease depends upon achieving therapeutic concentrations of medications, such as dexamethasone or gentamicin, within the fluids and tissues of the inner ear. Drugs delivered to the inner ear are commonly administered systemically via the oral, intravenous, or intramuscular routes. However, systemic drug administration for focal disease of the inner ear is not ideal as this does not meet an important pharmacological principal in which local administration is preferred for local pathological processes.
Systemic drug administration increases the likelihood of systemic toxicities and side effects and creates an inequality in drug concentration with higher circulating levels in the serum but lower local levels at the inner ear where the drug is needed. Relatively large doses of a medication are therefore required to overcome the systemic volume of distribution in order to achieve a therapeutic drug concentration in the inner ear. In addition to the inherent risk of toxicities, responses to systemic administration vary considerably between patients. This is due to inter-dose variability, differences in systemic volume of distribution, variability in the ability of a given drug to cross the blood-inner ear barrier, and factors affecting the half-life of the drug such as peripheral drug metabolism and drug clearance.
Intratympanic injection of streptomycin for the treatment of intractable vertigo in patients with Ménière's disease resulted in profound hearing loss in a significant proportion of patients. However, reported success in ameliorating Ménière's symptomology with intratympanic drug administration helped to popularize the concept of local drug administration to the inner ear. Indeed, it has become routine for otolaryngologists to perform intratympanic injections, and the efficacy of this approach versus systemic drug administration has been confirmed for various clinical indications.
However, there remains a considerable amount of variability in clinical outcomes among those patients treated with intratympanic injections. Several factors account for this variability. Drugs enter the fluids of the inner ear by diffusing across the round window membrane (RWM), the major site of absorption of medications from the middle ear into the inner ear. Unfortunately, large portions of the administered medication do not come into contact with the RWM. This portion of drug is instead absorbed by the mucosa of the middle ear or evacuated from the middle ear space by the eustachian tube. In either case, the drug is unavailable to diffuse into the inner ear. Therefore, the concentration of drug in the inner ear depends greatly upon the drug coming into contact with the RWM.